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Cell Host Microbe. 2015 Oct 14;18(4):456-62. doi: 10.1016/j.chom.2015.09.005.

Mammalian Lipopolysaccharide Receptors Incorporated into the Retroviral Envelope Augment Virus Transmission.

Author information

1
Department of Microbiology, The University of Chicago, Chicago, IL 60637, USA.
2
Division of Infectious Diseases and Immunology, Program in Innate Immunity, Department of Medicine, University of Massachusetts, Worcester, MA 01605, USA; Center of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway.
3
Department of Bioengineering and Therapeutic Sciences and California Institute of Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
4
Shock and Trauma Research Center, Medical School, University of Missouri, Kansas City, MO 64108, USA.
5
Department of Pathology, The University of Chicago, Chicago, IL 60637, USA.
6
Department of Microbiology, The University of Chicago, Chicago, IL 60637, USA. Electronic address: tgolovki@bsd.uchicago.edu.

Abstract

The orally transmitted retrovirus mouse mammary tumor virus (MMTV) requires the intestinal microbiota for persistence. Virion-associated lipopolysaccharide (LPS) activates Toll-like receptor 4 (TLR4), stimulating production of the immunosuppressive cytokine IL-10 and MMTV evasion of host immunity. However, the mechanisms by which MMTV associates with LPS remain unknown. We find that the viral envelope contains the mammalian LPS-binding factors CD14, TLR4, and MD-2, which, in conjunction with LPS-binding protein (LBP), bind LPS to the virus and augment transmission. MMTV isolated from infected mice lacking these LBPs cannot engage LPS or stimulate TLR4 and have a transmission defect. Furthermore, MMTV incorporation of a weak agonist LPS from Bacteroides, a prevalent LPS source in the gut, significantly enhances the ability of this LPS to stimulate TLR4, suggesting that MMTV intensifies these immunostimulatory properties. Thus, an orally transmitted retrovirus can capture, modify, and exploit mammalian receptors for bacterial ligands to ensure successful transmission.

PMID:
26468748
PMCID:
PMC4795803
DOI:
10.1016/j.chom.2015.09.005
[Indexed for MEDLINE]
Free PMC Article

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